There are various methods for restoring a damaged tissue or a pathogenic part of a living body. One method is to substitute the damaged tissue or pathogenic part with materials other than a living tissue, such as plastic, metal, and/or ceramic to restore the damaged tissue or the pathogenic part. Another method is to substitute the damaged tissue or pathogenic part with parts from other individuals or other animals, or from a different location of the living body, for example, skin. These methods can have certain drawbacks, including physical wear and dislodgement of non-living tissues and availability or suitability of living tissue for certain purposes. A third method is to generate a new vital tissue in vitro.
Accordingly, a method of restoring a damaged tissue or a pathogenic part of a living body is to substitute the damaged part of a tissue by a tissue that is obtained by cultivating a cell or tissue in vitro. It has recently been reported that such method is generally possible as may be applicable to many tissues such as skin, cartilage, bone, blood vessels, liver, and pancreas. If a cell or tissue derived from a living body is cultivated outside the living body of a patient, and the cell or tissue obtained by the culture is applied to the restoration of a damaged part, a tissue can be regenerated in the body. Further, if the tissue applied to the restoration is derived from the individual that is to receive the cultivated tissue, there is no concern of immunological rejection of the tissue upon its implantation into the individual.
Articular cartilage coating the ends of flexibly joined bones takes over the function of the load distribution in the loaded joint. For this function the cartilage tissue is capable of reversibly taking up water under conditions of low load or pressure and then releasing water under conditions of increased load or pressure. Furthermore, the cartilage surfaces serve as sliding surfaces in the joints.
Cartilage is not vascularized and its ability to regenerate in vivo is very limited, particularly in adult individuals and if the piece of cartilage to be regenerated exceeds even a small volume. However, articular cartilage often suffers degeneration due to wear, age, disease, or traumatic or overuse injuries, involving a significantly greater volume than might be naturally regenerated. This kind of defect of the cartilage layer makes movement and loading of the affected joint painful and can lead to further complications such as inflammation, which can contribute to further damage to the cartilage layer.
For these reasons efforts have been made for quite some time to replace or repair missing or damaged cartilage, especially articular cartilage.
Methods to repair defects involving articular cartilage alone or articular cartilage and the subchondral bone tissue beneath it by milling or drilling the defect location to form a bore of an as precise geometry as possible, extracting a disk of cartilage or cartilage and bone of the same geometry from a less weight bearing location of, e.g., the same joint by means of boring or punching, and inserting this column into the bore at the site of the defect to be treated. In the same manner, larger defects with several bores are repaired (mosaic plasty).
A number of methods have been developed in an attempt to produce cartilage at least partly in vitro, i.e., to produce cartilage using vital natural cells under artificial conditions. A problem encountered in these methods is the fact that chondrocytes in these in vitro conditions have the tendency to de-differentiate into fibroblasts relatively rapidly. By the de-differentiation the chondrocytes lose, inter alia, the ability to produce type II collagen which is one of the most important components of cartilage tissue. Attempts to address the problem of de-differentiation of chondrocytes in vitro have included immobilizing the chondrocytes in highly cell-dense cultures in a monolayer or in a three-dimensional scaffold. Under these conditions, chondrocytes reproduce themselves without substantial de-differentiation, and they form an extracellular matrix which is at least similar to the extracellular matrix of native cartilage. A three-dimensional scaffold is used not only for immobilizing the cells but also for imparting mechanical stability after implantation which is needed because none of the cartilage tissues produced in the above manner has a stability which can withstand even a low mechanical strain.